Month: July 2021

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 918321-20-7, name is Methyl 5-amino-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-carboxylate, A new synthetic method of this compound is introduced below., Quality Control of Methyl 5-amino-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-carboxylate

A mixture of Xantphos (1.20 g, 2.05 mmol) and tris(dibenzylideneacetone)dipalladium (0) (1.26 g, 1.37 mmol) in anhydrous anisole (76 mL) was stirred under nitrogen, at 50 0C for 30 minutes to provide a an orange- brown solution of the catalyst.[00326] To a stirred mixture of 6-amino-7-fluoro-3-methyl-3H-benzoimidazole-5- carboxylic acid methyl ester (6) (8.00 g, 34.16 mmol) and cesium carbonate (22.48 g, 68.31 mmol) in anhydrous anisole (76 mL) under nitrogen was added 4-bromo-2- chloroiodobenzene (1.60 g, 1.10 equiv., 4.88 mmol). The preformed catalyst, as prepared above, was then added to the mixture to provide a dark brown suspension, which was heated at 100 +/- 2 0C, with stirring at 350 rpm. The reaction was monitored by HPLC analysis. After 41 hours, no 6-amino-7-fluoro-3-methyl-3//-benzoimidazole-5-carboxylic acid methyl ester (6) remained. The reaction mixture was cooled to about 80 0C and IM sulfuric acid (40.99 mL 40.99 mmol) was added. Gas evolution was observed after 10 minutes and the rate of addition was controlled to moderate the effervescence. At the end of the addition the pH was between 7 and 8. Additional sulfuric acid (IM, 10.25 mL, 10.25 mmol) was then added to give mobile slurry with a pH of 0. The mixture was diluted with anisole (20 mL) and Celatom FW- 14 filter agent was added. It was then filtered at about 80 C through a water-wet pad of Celatom FW- 14 filter agent and the cake was washed with anisole (1 x 40 mL + 3 x 20 mL), then water (10 mL). The lower aqueous layer was separated and discarded and the organic layer was washed with 10 % aqueous NaCl solution (2 x 40 mL). This was added to a sodium hydroxide (5.46 g, 68.3 mmol) in methanol (24 mL) and the mixture was heated at 65 C with stirring. After 17.5 hours HPLC analysis indicated that the hydrolysis of the ester was complete and the slurry was cooled to 15 C, then filtered on a sinter. The solid was washed with water (4 x 24 mL), MTBE (24 mL), and acetonitrile (2 x 25 mL) and then dried at 45 0C in a vacuum oven to provide 11.07 g of 6-(4- EPO bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (7) as a fine pale brown solid (assay 93.7% by 1H NMR), actual wt 10.37 g (72.2% yield). 1H NMR (400 MHz, d6 DMSO) delta 3.85 (3H, s, NMe), 6.53 (IH, dd, J 9, 7, Ar-H), 7.27 (IH, dd, J 9S 2.5, Ar-H), 7.56 (IH, d, J 9, Ar-H), 7.97 (IH, s, Ar-H), 8.20 (IH5 s, Ar-H), 11.5 (IH, s, CO2H). 13C NMR (100 MHz, d6 DMSO) delta 31 (CH3), 108 (CH, d, J 2), 109 (CH), 117 (C, d, J6), 122 (C), 124 (C, d, J7), 127 (C)5 130 (C)5 131 (C), 132 (C, d, J9), 133 (C5 d, J l l), 141 (C), 145 (CF, d5 J 252), 146 (CH)5 170 (C=O).

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; ARRAY BIOPHARMA INC.; ASTRAZENECA AB; WO2007/2157; (2007); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 615-16-7, The chemical industry reduces the impact on the environment during synthesis 615-16-7, name is 2-Hydroxybenzimidazole, I believe this compound will play a more active role in future production and life.

Step 1: (0389) 1H-benzimidazol-2(3H)-one 19-a (500 mg, 3.73 mmol) was added into anhydrous aluminum chloride (1.98 g, 14.9 mmol) and tetrachloroethane (3 ml). Chloroacetyl chloride (843 mg, 7.46 mmol) dissolved in tetrachloroethane (3 ml) was added dropwise thereto under ice bath followed by stirring at 100 C. for 1 hour. The mixture was cooled to room temperature, ice and 4N hydrochloric acid (20 ml) were added sequentially followed by stirring for 6 hours, the precipitated solid was filtered, the filter cake was slurried in isopropanol, filtered, and dried to give 19-b as an off-white solid (730 mg, yield: 93%). EI-MS (m/z): 210.

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 2-Hydroxybenzimidazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES; SUZHOU VIGONVITA LIFE SCIENCES CO., LTD.; TOPHARMAN SHANDONG CO., LTD.; JIANG, Hualiang; WANG, Zhen; LI, Jianfeng; ZHANG, Rongxia; HE, Yang; LIU, Yongjian; BI, Minghao; LIU, Zheng; TIAN, Guanghui; CHEN, Weiming; YANG, Feipu; WU, Chunhui; WANG, Yu; JIANG, Xiangrui; YIN, Jingjing; WANG, Guan; SHEN, Jingshan; (70 pag.)US2017/158680; (2017); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 570-22-9, A common heterocyclic compound, 570-22-9, name is 1H-Imidazole-4,5-dicarboxylic acid, molecular formula is C5H4N2O4, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

General procedure: The complex was synthesized by hydrothermal method. A mixture of Zn(NO3)2.6H2O (0.47 g; 1.6 mmol), H3idc (0.25 g, 1.6 mmol) and water (30 mL) was sealed in a 45 mL Parr brand teflon-linedacid digestion bomb and heated at 180 C for 5 days, and then cooled to room temperature at a rate of 5 C/h.

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Article; Erer, Hakan; Ye?ilel, Okan Zafer; ?ahin, Onur; Bueyuekguengoer, Orhan; Inorganica Chimica Acta; vol. 434; (2015); p. 14 – 23;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 288-32-4, name is 1H-Imidazole, A new synthetic method of this compound is introduced below., Recommanded Product: 1H-Imidazole

Take 7kg sodium hydride DMF solution with 20% concentration, add 7kg 20% imidazole DMF solution under ice-cooling at a speed of 2ml/s with stirring, stir at 60C for 60min; use ice salt After the bath is cooled, 5 kg of 1-chloro-4-(4-chlorophenyl)-2-butanol is slowly added, and the reaction is stirred at 60 C. for 120 min. After cooling with an ice bath, the reaction solution is obtained; in the reaction 25% by weight of n-hexane was added to the solution, stirred for 15 minutes at 3 revolutions per second, and then added to the solution.35 wt% of ice water was stirred at 3 rev/s until the precipitation stopped. After filtration, the cake was washed once with water 1/3 times the weight of the cake, and dried at 2825 r/min. After 60 minutes, ethyl acetate and activated charcoal were used 2.5 times and 0.05 times the weight of the centrifugally dried product, respectively, and allowed to stand at -5 C. for 13 hours to recrystallize, and the recrystallized product was dried at 50 C., ie, 1-(2-Hydroxy-4-(4-chlorophenyl)butyl)-1H-imidazole, purity99.31%.

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; Zhuzhou Qianjin Pharmaceutical Co., Ltd.; Li Sanxin; Peng Kaifeng; Ling Yonggen; Wen Fengqiu; Gong Yun; Li Fujun; (13 pag.)CN105198818; (2018); B;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 50995-95-4, name is 2-Propylimidazole, A new synthetic method of this compound is introduced below., Safety of 2-Propylimidazole

Add 2,4-dichloropyrimidine (3.000 g, 20.2 mmol), 2-propylimidazole (2.662 g, 24.2 mmol) and potassium carbonate (4.168 g, 30.3 mmol)Add it to a round bottom flask (100 mL), using acetonitrile (40 mL) as a solvent,The reaction was carried out at 50 C for 11 hours. TLC was followed until the reaction was complete,Cooled to room temperature, distilled under reduced pressure,Purification by column chromatography to obtain white solid intermediate III-7(1.453 g), yield: 32.4%.

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; Southwest University; Zhou Chenghe; Wang Ya; Li Ruixue; Wang Jie; Geng Rongxia; (21 pag.)CN110452224; (2019); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 17228-38-5 as follows. Safety of N-Methyl-1H-benzo[d]imidazol-2-amine

Example 2.03 can also be prepared as follows:(3R)-4-(2-Chloro-6-(1-((R)-S-methylsulfonimidoyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine (179 mg, 0.54 mmol), N-methyl-1H-benzo[d]imidazol-2-amine (159 mg, 1.08 mmol) and cesium carbonate (529 mg, 1.62 mmol) were suspended in DMA (2 ml) and sealed into a microwave tube. The reaction mixture was heated to 80 C. for 90 minutes in a microwave reactor and then cooled to RT. The reaction mixture was filtered and then purified by preparative HPLC, using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to afford a solid (55.0 mg). In an additional procedure: (R)-4-(2-Chloro-6-(1-((R)-S-methylsulfonimidoyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine (89 mg, 0.27 mmol), N-methyl-1H-benzo[d]imidazol-2-amine (79 mg, 0.54 mmol) and cesium carbonate (263 mg, 0.81 mmol) were suspended in DMA (2 ml) and sealed into a microwave tube. The reaction mixture was heated to 80 C. for 5 hours in a microwave reactor and then cooled to RT. The reaction mixture was filtered, and combined with the solid from the previous procedure and then purified by preparative HPLC using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated and the residue was purified by preparative HPLC using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated and the residue purified again by preparative HPLC using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to afford the title compound (38.4 mg, 32%); 1H NMR (400 MHz, DMSO-d6) 1.29 (3H, d), 1.52 (3H, m), 1.72-1.86 (1H, m), 3.02 (3H, s), 3.03 (3H, d), 3.26-3.33 (1H, m), 3.52 (1H, t), 3.66 (1H, d), 3.80 (1H, d), 4.01 (2H, m), 4.12 (1H, s, obscured by methanol peak), 4.51 (1H, s), 6.77 (1H, s), 6.98 (1H, t), 7.09 (1H, t), 7.25 (1H, d), 8.08 (1H, d), 8.71 (1H, d); m/z: (ES+) MH+, 442.16. Chiral HPLC: (HP1100 System 4, 20 mum Chiralpak AS (250 mm×4.6 mm) column eluting with iso-Hexane/IPA/TEA 70/30/0.1) Rf, 11.984 97.9%.

According to the analysis of related databases, 17228-38-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ASTRAZENECA AB; US2011/306613; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 288-32-4, name is 1H-Imidazole, molecular formula is C3H4N2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. name: 1H-Imidazole

General procedure: NH-containing heterocycle (1.4 mmol) and DMF (2.0 mL) were added to a mixture of CuCl (15.0 mol%) and ligand 1 (20.0 mol%) in DMF (2.0 mL), aryl iodide (1.0 mmol), NaOH (2.0 mmol). The mixture was vigorously stirred at 120 C for 14 h under a dry nitrogen atmosphere. After completion of the reaction (as monitored by TLC), H2O was added and the organic layer was extracted with EtOAc, washed with brine and dried over MgSO4. The solution was filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography. The purity of the compounds was checked by 1H NMR and yields are based on aryl iodide. All the products are known and the spectroscopic data (FT-IR and NMR) and melting points were consistent with those reported in the literature.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 288-32-4, its application will become more common.

Reference:
Article; Sajadi, S. Mohammad; Maham, Mehdi; Journal of Chemical Research; vol. 38; 2; (2014); p. 128 – 129;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 7189-69-7, name is 1,1′-Sulfonyldiimidazole, belongs to imidazoles-derivatives compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 7189-69-7, Product Details of 7189-69-7

To a pre-washed (hexane) suspension of NaH (60% in mineraloil, 284 mg, 7.11 mmol) in dry DMF (10 mL), a soln of 7 (1.06 g,1.42 mmol) in dry DMF (15 mL) was slowly added under argonatmosphere at 0 C. The mixture was stirred at 0 C for 30 min,cooled to 30 C, treated with Im2SO2 (411.5 mg, 2.08 mmol) andfurther stirred at 30 C. After 1 h, TLC analysis (4:6 hexane-EtOAc) revealed the complete disappearance of the starting material.The reaction mixture was then cooled to 40 C, the excess ofNaH was destroyed by addition of MeOH (0.5 mL). After 10 min,Et2O (20 mL) and crushed iced-water were added. The organicphase was separated and the aqueous layer was extracted withEt2O (3 50 mL). The collected organic phases were dried, filtered,and concentrated under diminished pressure. Flash chromatographicpurification over silica gel of the reaction product (6:4 hexane-EtOAc) gave pure 8 (1.02 g, 83% yield) as a clear syrup; Rf 0.37(6:4 hexane-EtOAc), [a]D 13.6 (c 1.16, CHCl3); 1H NMR (CD3CN): d8.01 (dd, 1H, J2,4 1.3 Hz, Im-H2), 7.46 (dd, 1H, J2,5 0.9 Hz, J4,5 1.6 Hz,Im-H4), 7.40-7.24 (m, 15H, Ar-H), 7.01 (dd, 1H, Im-H5), 5.25 (dd,1H, J10,20 0.6 Hz, J20,30 2.3 Hz, H-20), 4.94 (d, 1H, H-10), 4.68, 4.48(AB system, 2H, JA,B 10.8 Hz, CH2Ph), 4.64, 4.49 (AB system, 2H,JA,B 11.8 Hz, CH2Ph), 4.56, 4.47 (AB system, 2H, JA,B 11.9 Hz, CH2Ph),4.35 (m, 2H, H-1, H-2), 4.20 (dt, 1H, J4,5 4.9 Hz, J5,6a = J5,6b 6.4 Hz,H-5), 4.03 (dd, 1H, J2,3 7.3 Hz, J3,4 1.9 Hz, H-3), 3.94 (m, 2H, H-6a,H-6b), 3.89 (dd, 1H, H-4), 3.70 (dd, 1H, J30,40 10.5 Hz, H-30), 3.68(m, 3H, H-40 , H-60a, H60b), 3.39 (m, 1H, H-50), 3.38, 3.35 (2s, each3H, 2 OMe-1), 1.35, 1.34, 1.32, 1.29 (4s, each 3H, 2 CMe2);13C NMR (CD3CN): d 139.3, 139.1, 138.4 (3 Ar-C), 138.1 (Im-C2),131.2 (Im-C4), 129.3-128.6 (Ar-CH), 119.7 (Im-C5), 110.5, 109.0(2 CMe2), 106.3 (C-1), 99.0 (C-10), 84.6 (C-20), 78.7 (C-4), 78.0

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1,1′-Sulfonyldiimidazole, and friends who are interested can also refer to it.

Reference:
Article; Guazzelli, Lorenzo; Catelani, Giorgio; D’Andrea, Felicia; Gragnani, Tiziana; Carbohydrate Research; vol. 388; 1; (2014); p. 44 – 49;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 53484-15-4,Some common heterocyclic compound, 53484-15-4, name is 5-Bromo-1-methyl-1H-benzo[d]Imidazole, molecular formula is C8H7BrN2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Into a 100-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of (S)-(4-(4-(tert-butoxycarbonyl)-3-methylpiperazine-l- carbonyl)-3-fluorophenyl)boronic acid (837 mg, 2.29 mmol, 1.00 equiv) in toluene (20 mL), 5-bromo-l-methyl- lH-l,3-benzodiazole (400 mg, 1.90 mmol, 0.83 equiv), Pd(PPh3)4 (264 mg, 0.23 mmol, 0.10 equiv), sodium carbonate(2M, 10 mL), ethanol (2.8 mL). The resulting mixture was stirred overnight at 95C. After cooled to room temperature, the resulting solution was diluted with 20 mL of H20, extracted with 3×30 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (90: 10). The collected fractions were combined and concentrated under vacuum. This resulted in 800 mg (77%) of the title compound as a brown solid. LC-MS (ES, m/z) 453 [M+H]+

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromo-1-methyl-1H-benzo[d]Imidazole, its application will become more common.

Reference:
Patent; FORMA THERAPEUTICS, INC.; BAIR, Kenneth, W.; LANCIA, David, R.; LI, Hongbin; LOCH, James; LU, Wei; MARTIN, Matthew, W.; MILLAN, David, S.; SCHILLER, Shawn, E.r.; TEBBE, Mark, J.; WO2014/164749; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 14741-71-0,Some common heterocyclic compound, 14741-71-0, name is Ethyl 2-(1H-benzo[d]imidazol-2-yl)acetate, molecular formula is C11H12N2O2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

General procedure: Et3N(4 mmol) was added dropwise to a stirred solution of the benzimidazole (1.5 mmol) and the dichloride compound 1(2 mmol) in CH2Cl2 (3 mL) at 0 C. The resulting mixture was stirred at room temperature overnight and worked up as for Method A.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Ethyl 2-(1H-benzo[d]imidazol-2-yl)acetate, its application will become more common.

Reference:
Article; Innes, Dylan; Perkins, Michael V.; Liepa, Andris J.; Francis, Craig L.; Australian Journal of Chemistry; vol. 71; 1; (2018); p. 58 – 69;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem